Meta-analyses of breast cancer trials:
problems with subgroup analyses
Richard Peto, CTSU
University of Oxford, UK
EBCTCG, Lancet 2011
Local and systemic therapies:
several MODERATE survival gains
MODERATE improvements in early detection,
in local control, in chemotherapy and in
endocrine therapy have, in aggregate,
SUBSTANTIALLY reduced national mortality rates
EBCTCG, Lancet 2011
Reliable assessment of MODERATE
differences in LONG-TERM survival
by the 5-yearly worldwide overview
(with tens of thousands randomised)
Need all the main randomised trial results,
both to get big enough numbers and to
avoid undue emphasis on particular studies
EBCTCG, Lancet 2011
Early Breast Cancer Trialists’
Collaborative Group (EBCTCG)
So as not to miss any MODERATE
differences in long-term survival,
the world’s trialists have shared
their data every 5 years since 1985
1985, 1990, 1995, 2000, 2005, 2010 (2015)
EBCTCG, Lancet 2011
620 names of EBCTCG collaborators in local and systemic therapy trials,
listed alphabetically by institution, then name. Lancet 2011; 378: 771-84.
ACETBC, Tokyo, Japan O Abe, R Abe, K Enomoto, K Kikuchi, H Koyama, H Masuda, Y Nomura,
Y Ohashi, K Sakai, K Sugimachi, M Toi, T Tominaga, J Uchino, M Yoshida. Addenbrooke’s Hospital,
Cambridge, UK J L Haybittle. Anglo-Celtic Cooperative Oncology Group, UK C F Leonard. ARCOSEIN
Group, France G Calais, P Geraud. ATLAS Trial Collaborative Study Group, Oxford, UK V Collett,
C Davies, A Delmestri, J Sayer. Auckland Breast Cancer Study Group, New Zealand V J Harvey,
I M Holdaway, R G Kay, B H Mason. Australian New Zealand Breast Cancer Trials Group, Sydney,
Australia J F Forbes, N Wilcken. Austrian Breast Cancer Study Group, Vienna, Austria R Bartsch,
P Dubsky, C Fesl, H Fohler, M Gnant, R Greil, R Jakesz, A Lang, G Luschin-Ebengreuth, C Marth,
B Mlineritsch, H Samonigg, C F Singer, G G Steger, H Stoger. Beatson Oncology Centre, Glasgow,
UK P Canney, H M A Yosef. Belgian Adjuvant Breast Cancer Project, Liège, Belgium C Focan. BerlinBuch Akademie der Wissenschaften, Germany U Peek. Birmingham General Hospital, UK
G D Oates, J Powell. Bordeaux Institut Bergonié, France M Durand, L Mauriac. Bordet Institute,
Brussels, Belgium A Di Leo, S Dolci, D Larsimont, J M Nogaret, C Philippson, M J Piccart. Bradford
Royal Infirmary, UK M B Masood, D Parker, J J Price. Breast Cancer International Research Group
(BCIRG) M A Lindsay, J Mackey, M Martin. Breast Cancer Study Group of the Comprehensive
Cancer Centre, Limburg, Netherlands P S G J Hupperets. British Association of Surgical Oncology
BASO II Trialists, London, UK T Bates, R W Blamey, U Chetty, I O Ellis, E Mallon, D A L Morgan,
J Patnick, S Pinder. British Columbia Cancer Agency, Vancouver, Canada I Olivotto, J Ragaz. Cancer
and Leukemia Group B, Washington DC, USA D Berry, G Broadwater, C Cirrincione, H Muss,
L Norton, R B Weiss. Cancer Care Ontario, Canada H T Abu-Zahra. Cancer Research Centre of the
Russian Academy of Medical Sciences, Moscow, Russia S M Portnoj. Cancer Research UK Clinical
Trials Unit (CRCTU), NCRI, Birmingham, UK S Bowden, C Brookes, J Dunn, I Fernando, M Lee,
C Poole, D Rea, D Spooner. Cardiff Trialists Group, UK P J Barrett-Lee, R E Mansel, I J Monypenny.
Case Western Reserve University, Cleveland, OH, USA N H Gordon. Central Oncology Group,
Milwaukee, WI, USA H L Davis. Centre for Cancer Prevention, Wolfson Institute of Preventive
Medicine, Queen Mary, University of London, UK J Cuzick. Centre Léon-Bérard, Lyon, France
Y Lehingue, P Romestaing. Centre Paul Lamarque, Montpellier, France J B Dubois. Centre Regional
François Baclesse, Caen, France T Delozier, B Griffon, J Mace Lesec’h. Centre René Huguenin,
Paris, St Cloud, France P Rambert. Centro Oncologico, Trieste, Italy G Mustacchi. Charles
University in Prague, First Faculty of Medicine, Department of Oncology of the First Faculty of
Medicine and General Teaching Hospital, Czech Republic L Petruzelka, O Pribylova. Cheltenham
General Hospital, UK J R Owen. Chemo N0 Trial Group, Germany N Harbeck, F Janicke, C Meisner,
M Schmitt, C Thomssen. Chicago University, IL, USA P Meier. Chinese Academy of Medical
Sciences, Beijing, People’s Republic of China (in collaboration with the Oxford CTSU) Y Shan,
Y F Shao, X Wang, D B Zhao (CTSU: Z M Chen, H C Pan). Christie Hospital and Holt Radium
Institute, Manchester, UK A Howell, R Swindell. Clinical Trial Service Unit, Oxford, UK (ie, EBCTCG
Secretariat) J A Burrett, M Clarke, R Collins, C Correa, D Cutter, S Darby, C Davies, K Davies,
A Delmestri, P Elphinstone, V Evans, L Gettins, J Godwin, R Gray, C Gregory, D Hermans, C Hicks,
S James, A Kerr, E MacKinnon, M Lay, P McGale, T McHugh, R Peto, J Sayer, C Taylor, Y Wang.
Coimbra Instituto de Oncologia, Portugal J Albano, C F de Oliveira, H Gervasio, J Gordilho.
Copenhagen Radium Centre, Denmark H Johansen, H T Mouridsen. Dana-Farber Cancer Institute,
Boston, MA, USA R S Gelman, J R Harris, D Hayes, C Henderson, C L Shapiro, E Winer. Danish
Breast Cancer Cooperative Group, Copenhagen, Denmark P Christiansen, B Ejlertsen, M Ewertz,
M-B Jensen, S Moller, H T Mouridsen. Danish Cancer Registry, Copenhagen, Denmark
B Carstensen, T Palshof. Düsseldorf University, Germany H J Trampisch. Dutch Working Party for
Autologous Bone Marrow Transplant in Solid Tumours, Amsterdam & Groningen, Netherlands
O Dalesio, E G E de Vries, S Rodenhuis, H van Tinteren. Eastern Cooperative Oncology Group,
Boston, MA, USA R L Comis, N E Davidson, R Gray, N Robert, G Sledge, L J Solin, J A Sparano,
D C Tormey, W Wood. Edinburgh Breast Unit, UK D Cameron, U Chetty, J M Dixon, P Forrest,
W Jack, I Kunkler. Elim Hospital, Hamburg, Germany J Rossbach. Erasmus MC/Daniel den Hoed
Cancer Center, Rotterdam, Netherlands J G M Klijn, A D Treurniet-Donker, W L J van Putten.
European Institute of Oncology, Milan, Italy N Rotmensz, U Veronesi, G Viale. European
Organization for Research and Treatment of Cancer, Brussels, Belgium H Bartelink, N Bijker,
J Bogaerts, F Cardoso, T Cufer, J P Julien, E Rutgers, C J H van de Velde. Evanston Hospital, IL, USA
M P Cunningham. Finnish Breast Cancer Group, Finland R Huovinen, H Joensuu. Fondazione
Maugeri Pavia, Italy A Costa, C Tinterri. Fondazione Michelangelo, Milan, Italy G Bonadonna,
L Gianni, P Valagussa. Fox Chase Cancer Center, Philadelphia, PA, USA L J Goldstein. French
Adjuvant Study Group (GFEA), Guyancourt, France J Bonneterre, P Fargeot, P Fumoleau,
P Kerbrat, E Luporsi, M Namer. German Adjuvant Breast Group (GABG), Frankfurt, Germany
W Eiermann, J Hilfrich, W Jonat, M Kaufmann, R Kreienberg, M Schumacher.
German Breast Cancer Study Group (BMFT), Freiburg, Germany G Bastert, H Rauschecker,
R Sauer, W Sauerbrei, A Schauer, M Schumacher. German Breast Group (GBG),
NeuIsenburg, Germany J U Blohmer, S D Costa, H Eidtmann, B Gerber, C Jackisch, S Loibl,
G von Minckwitz. Ghent University Hospital, Belgium A de Schryver, L Vakaet. GIVIO
Interdisciplinary Group for Cancer Care Evaluation, Chieti, Italy M Belfiglio, A Nicolucci,
F Pellegrini, M C Pirozzoli, M Sacco, M Valentini. Glasgow Victoria Infirmary, UK
C S McArdle, D C Smith, S Stallard. Groote Schuur Hospital, Cape Town, South Africa
D M Dent, C A Gudgeon, A Hacking, E Murray, E Panieri, ID Werner. Grupo Español de
Investigación en Cáncer de Mama (GEICAM), Spain E Carrasco, M Martin, M A Segui.
Gruppo Oncologico Clinico Cooperativo del Nord Est, Aviano, Italy E Galligioni. Gruppo
Oncologico Dell’Italia Meridionale (GOIM), Rome, Italy M Lopez. Guadalajara Hospital de
20 Noviembre, Mexico A Erazo, J Y Medina. Gunma University, Japan J Horiguchi, H Takei.
Guy’s Hospital, London, UK I S Fentiman, J L Hayward, R D Rubens, D Skilton. Heidelberg
University I, Germany H Scheurlen. Heidelberg University II, Germany M Kaufmann,
H C Sohn. Helios Klinikum Berlin-Buch, Germany M Untch. Hellenic Breast Surgeons Society,
Greece U Dafni, C Markopoulos. Hellenic Cooperative Oncology Group, Athens, Greece
U Dafni, G Fountzilas. Hellenic Oncology Research Group, Greece D Mavroudis. Helsinki
Deaconess Medical Centre, Finland P Klefstrom. Helsinki University, Finland C Blomqvist,
T Saarto. Hospital del Mar, Barcelona, Spain M Gallen. Innsbruck University, Austria
R Margreiter. Institut Claudius Regaud, Toulouse, France B de Lafontan, J Mihura, H Roche.
Institut Curie, Paris, France B Asselain, R J Salmon, J R Vilcoq. Institut Gustave-Roussy, Paris,
France R Arriagada, C. Bourgier, C Hill, S Koscielny, A Laplanche, M G Le, M Spielmann.
Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU, NCRI), UK R
A’Hern, J Bliss, P Ellis, L Kilburn, J R Yarnold. Integraal Kankercentrum, Amsterdam,
Netherlands J Benraadt, M Kooi, A O van de Velde, J A van Dongen, J B Vermorken.
International Breast Cancer Study Group (IBCSG), Bern, Switzerland M Castiglione, A Coates,
M Colleoni, J Collins, J Forbes, R D Gelber, A Goldhirsch, J Lindtner, K N Price, M M Regan,
C M Rudenstam, H J Senn, B Thuerlimann. International Collaborative Cancer Group,
Charing Cross Hospital, London, UK J M Bliss, C E D Chilvers, R C Coombes, E Hall, M Marty.
International Drug Development Institute, Louvain-la-Neuve, Belgium M Buyse.
International TABLE Study Group, Berlin, Germany K Possinger, P Schmid, M Untch,
D Wallwiener. ISD Cancer Clinical Trials Team (incorporating the former Scottish Cancer
Therapy Network), Edinburgh, UK L Foster, W D George, H J Stewart, P Stroner. Israel
NSABC, Tel Aviv, Israel R Borovik, H Hayat, M J Inbar, E Robinson. Istituto Nazionale per la
Ricerca sul Cancro, Genova, Italy P Bruzzi, L Del Mastro, P Pronzato, M R Sertoli,
M Venturini. Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy T Camerini,
G De Palo, M G Di Mauro, F Formelli, P Valagussa. Istituto Oncologico Romagnolo, Forli,
Italy D Amadori. Italian Cooperative Chemo-Radio-Surgical Group, Bologna, Italy A Martoni,
F Pannuti. Italian Oncology Group for Clinical Research (GOIRC), Parma, Italy R Camisa,
G Cocconi, A Colozza, R Passalacqua. Japan Clinical Oncology Group– Breast Cancer Study
Group, Matsuyama, Japan K Aogi, S Takashima. Japanese Foundation for Multidisciplinary
Treatment of Cancer, Tokyo, Japan O Abe, T Ikeda, K Inokuchi, K Kikuchi, K Sawa. Kawasaki
Medical School, Japan H Sonoo. Krakow Institute of Oncology, Poland S Korzeniowski,
J Skolyszewski. Kumamoto University Group, Japan M Ogawa, J Yamashita. Leiden
University Medical Center, Netherlands E Bastiaannet, C J H van de Velde, W van de Water,
J G H van Nes. Leuven Akademisch Ziekenhuis, Gasthuisberg, Belgium R Christiaens,
P Neven, R Paridaens, W Van den Bogaert. Ludwig-Maximilians University, Munich,
Germany S Braun, W Janni. Marseille Laboratoire de Cancérologie Biologique APM, France
P Martin, S Romain. Medical University Vienna – General Hospital - Department of
Obstetrics and Gynaecology and Department of Medicine I, Vienna, Austria M Janauer,
M Seifert, P Sevelda, C C Zielinski. Memorial Sloan-Kettering Cancer Center, New York, NY,
USA T Hakes, C A Hudis, L Norton, R Wittes. Metaxas Memorial Cancer Hospital, Athens,
Greece G Giokas, D Kondylis, B Lissaios. Mexican National Medical Center, Mexico City,
Mexico R de la Huerta, M G Sainz. National Cancer Institute, Bethesda, MD, USA R Altemus,
K Camphausen, K Cowan, D Danforth, A Lichter, M Lippman, J O’Shaughnessy, L J Pierce,
S Steinberg, D Venzon, J A Zujewski. National Cancer Institute of Bari, Italy C D’Amico,
M Lioce, A Paradiso. NCIC Clinical Trials Group, Kingston, Ontario, Canada J-A W Chapman,
K Gelmon, P E Goss, M N Levine, R Meyer, W Parulekar, J L Pater, K I Pritchard,
L E Shepherd, D Tu, T Whelan. National Kyushu Cancer Center, Japan Y Nomura, S Ohno.
National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA
S Anderson, G Bass, A Brown (deceased), J Bryant (deceased), J Costantino, J Dignam,
B Fisher, C Geyer, E P Mamounas, S Paik, C Redmond, S Swain, L Wickerham, N Wolmark.
Nolvadex Adjuvant Trial Organisation, London, UK M Baum, I M Jackson (deceased),
M K Palmer. North Central Cancer Treatment Group, Mayo Clinic, Rochester, MN, USA
E Perez, J N Ingle, V J Suman. North Sweden Breast Cancer Group, Umeå, Sweden
N O Bengtsson, S Emdin, H Jonsson. North-West Oncology Group (GONO), Italy L Del Mastro,
M Venturini. North-Western British Surgeons, Manchester, UK J P Lythgoe, R Swindell.
Northwick Park Hospital, London, UK M Kissin. Norwegian Breast Cancer Group, Oslo, Norway
B Erikstein, E Hannisdal, A B Jacobsen, J E Varhaug. Norwegian Radium Hospital, Oslo,
Norway B Erikstein, S Gundersen, M Hauer-Jensen, H Host, A B Jacobsen, R Nissen-Meyer.
Nottingham City Hospital, UK R W Blamey, A K Mitchell, D A L Morgan, J F R Robertson. Oita
Prefectural Hospital, Japan H Ueo. Oncofrance, Paris, France M Di Palma, G Mathe
(deceased), J L Misset. Ontario Clinical Oncology Group, Hamilton, Canada M Levine,
K I Pritchard, T Whelan. Osaka City University, Japan K Morimoto. Osaka National Hospital,
Japan K Sawa, Y Takatsuka. Oxford Radcliffe Hospitals NHS Trust, Churchill Hospital, Oxford,
UK E Crossley, A Harris, D Talbot, M Taylor. PACS Adjuvant Study Group, France A L Martin,
H Roche. Parma Hospital, Italy G Cocconi, B di Blasio. Petrov Research Institute of Oncology,
St Petersburg, Russia V Ivanov, R Paltuev, V Semiglazov. Piedmont Oncology Association,
Winston-Salem, NC, USA J Brockschmidt, M R Cooper. Pretoria University, South Africa
C I Falkson. Royal Marsden NHS Trust, London and Sutton, UK R A’Hern, S Ashley, M
Dowsett, A Makris, T J Powles, I E Smith, J R Yarnold. St George’s Hospital, London, UK J C
Gazet. St George Hospital, Sydney, Australia L Browne, P Graham. St Luke’s Hospital, Dublin,
Ireland N Corcoran. Sardinia Oncology Hospital A Businico, Cagliari, Sardinia N Deshpande,
L di Martino. SASIB International Trialists, Cape Town, South Africa P Douglas, A Hacking,
H Host, A Lindtner, G Notter. Saskatchewan Cancer Foundation, Regina, Canada A J S Bryant,
G H Ewing, L A Firth, J L Krushen-Kosloski. Scandinavian Adjuvant Chemotherapy Study Group,
Oslo, Norway R Nissen-Meyer. South Sweden Breast Cancer Group, Lund, H Anderson,
F Killander, P Malmstrom, L Ryden. South-East Sweden Breast Cancer Group, Linköping,
Sweden L-G Arnesson, J Carstensen, M Dufmats, H Fohlin, B Nordenskjold, M Soderberg.
South-Eastern Cancer Study Group and Alabama Breast Cancer Project, Birmingham, AL, USA
J T Carpenter. Southampton Oncology Centre, UK N Murray, G T Royle, P D Simmonds.
Southwest Oncology Group, San Antonio, TX, USA K Albain, W Barlow, J Crowley, D Hayes,
J Gralow, S Green, G Hortobagyi, R Livingston, S Martino, C K Osborne, P M Ravdin.
Stockholm Breast Cancer Study Group, Sweden J Adolfsson, J Bergh, T Bondesson, F
Celebioglu, K Dahlberg, T Fornander, I Fredriksson, J Frisell, E Goransson, M Iiristo, U
Johansson, E Lenner, L Lofgren, P Nikolaidis, L Perbeck, S Rotstein, K Sandelin, L Skoog, G
Svane, E af Trampe, C Wadstrom. Swiss Group for Clinical Cancer Research (SAKK), Bern, and
OSAKO, St Gallen, Switzerland M Castiglione, A Goldhirsch, R Maibach, H J Senn, B
Thurlimann. Tampere University Hospital, Finland M Hakama, K Holli, J Isola, K Rouhento, R
Saaristo. Tel Aviv University, Israel H Brenner, A Hercbergs. The High-Dose Chemotherapy for
Breast Cancer Study Group (PEGASE), France A L Martin, H Roche. Tokyo Cancer Institute
Hospital, Japan M Yoshimoto. Toronto-Edmonton Breast Cancer Study Group, Canada A H G
Paterson, K I Pritchard. Toronto Princess Margaret Hospital, Canada A Fyles, J W Meakin, T
Panzarella, K I Pritchard. Tunis Institut Salah Azaiz, Tunisia J Bahi. UK Multicentre Cancer
Chemotherapy Study Group, London, UK M Reid, M Spittle. UK/ANZ DCIS Trial H Bishop, N J
Bundred, J Cuzick, I O Ellis, I S Fentiman, J F Forbes, S Forsyth, W D George, S E Pinder, I
Sestak. UK/Asia Collaborative Breast Cancer Group, London, UK G P Deutsch, R Gray, D L W
Kwong, V R Pai, R Peto, F Senanayake. University and Istituto Nazionale per la Ricerca sul
Cancro, Genoa, Italy on behalf of GROCTA trialists F Boccardo, A Rubagotti. University College
London, UK M Baum, S Forsyth, A Hackshaw, J Houghton, J Ledermann, K Monson, JS Tobias.
University Federico II, Naples, Italy C Carlomagno, M De Laurentiis, S De Placido.
University of Edinburgh, UK L Williams. University of Michigan, USA D Hayes, L J Pierce.
University of Texas MD Anderson Cancer Center, Houston, TX, USA K Broglio, A U Buzdar.
University of Wisconsin, USA R R Love. Uppsala-Örebro Breast Cancer Study Group, Sweden
J Ahlgren, H Garmo, L Holmberg, G Liljegren, H Lindman, F Warnberg. US Oncology, Houston,
USA L Asmar, S E Jones. West German Study Group (WSG), Germany O Gluz, N Harbeck,
C Liedtke, U Nitz. West of Scotland Breast Trial Group, Glasgow, UK A Litton. West Sweden
Breast Cancer Study Group, Gothenburg, Sweden A Wallgren, P Karlsson, B K Linderholm.
Western Cancer Study Group, Torrance, CA, USA R T Chlebowski. Würzburg University,
Germany H Caffier.
EBCTCG, Lancet 2011
Selected EBCTCG results, Lancet 2011-12,
emphasising subgroup difficulties that arose
even with tens of thousands randomised
- Radiotherapy
- Hormonal therapy
- Chemotherapy
Effects of giving radiotherapy (RT) to a
conserved breast: 10,000 randomised
Recurrence
Breast cancer mortality
Confidential preliminary results September 2010. Not for citation or publication
8
Hormonal therapy in ER+ disease
(i) ~5 years of tamoxifen vs not:
10,000 randomised in older trials
(+20,000 more in trials of
1-2 yrs v nil or 5 vs 1-2 yrs)
(ii) 5 years of (AI vs tamoxifen):
20,000 randomised in newer trials
Tamoxifen in ER+ disease, BREAST CANCER MORTALITY
1-2 yrs tam vs Not, HR 0.81±0.03
~5 vs 1-2 yrs tam, HR 0.87±0.04
Chemotherapy in ER+ disease
(i) Any anthracycline-based chemo (eg, 4AC)
vs no adjuvant chemotherapy, ER- or ER+:
10,000 randomised in older trials
(ii) Adding a taxane
(eg, 4AC ± 4Taxane vs 4AC alone):
10,000 randomised in newer trials
Any anthracycline-based regimen (eg, standard 4AC)
vs no adjuvant chemotherapy, by ER status
ER-Negative
ER-Positive
EBCTCG, Lancet 2011
Any anthracycline-based regimen (eg, standard 4AC)
vs no adjuvant chemotherapy, by ER status
ER-Negative
ER-Positive
EBCTCG, Lancet 2011
Direct and indirect comparisons between
different polychemotherapy regimens,
based on ~100,000 randomised women
45,000 taxane vs no taxane*
(44,000 with anthracycline in both arms)
22,000 anthracycline vs CMF
(18,000 vs “standard” CMF)
5,000 more vs less anthracycline
(2000 comparing currently relevant doses)
31,000 polychemotherapy vs no adjuvant chemo
(13,000 CMF vs Nil; 10,000 anthr.-based regimen vs Nil)
* Excludes trials of one taxane regimen vs another
EBCTCG, Lancet 2011
Taxane trials
Data on 44,000 women in randomised trials of a
taxane-plus-anthracycline-based regimen vs the
SAME, or MORE, non-taxane chemotherapy
11,000 in trials where the non-taxane regimen was
the SAME, and 33,000 in trials where it was MORE
[15% node-negative; mean follow-up only 5 years;
mean recurrence rate about 5% per year]
EBCTCG, Lancet 2011
Taxane-plus-anthracycline-based regimens vs
(L) the SAME, or (R) MORE, non-taxane chemo.
EBCTCG, Lancet 2011
Taxane trials: subgroup analyses
by age, stage and ER status
Taxane-plus-anthracycline-based regimen
vs
an anthracycline-based control regimen
with the SAME, or MORE, of each
non-taxane cytotoxic drug
EBCTCG, Lancet 2011
Taxane-plus-anthracycline-based regimen
vs the SAME, or MORE, non-taxane chemo,
by ENTRY AGE
EBCTCG, Lancet 2011
Taxane-plus-anthracycline-based regimen
vs the SAME, or MORE, non-taxane chemo,
by STAGE, ie, NODAL STATUS before chemotherapy
EBCTCG, Lancet 2011
Breast cancer mortality ratio in taxane trials,
by AGE and STAGE
EBCTCG, Lancet 2011
Breast cancer mortality ratio in taxane trials,
by ER STATUS and subsets of ER+
EBCTCG, Lancet 2011
Older chemo comparisons –
anthracycline-based regimens
and/or standard CMF,
by ER, age and stage
EBCTCG, Lancet 2011
ER+ disease, by age: Chemo-endocrine therapy vs same endocrine therapy alone
(chemo = anthracycline-based regimen or standard CMF, endocrine is for 5 years)
ER+, age <55
ER+, age 55-69
EBCTCG, Lancet 2011
Anthracycline-based regimens with higher
cumulative dosage (eg CAF/CEF) vs standard CMF
EBCTCG, Lancet 2011
Reduction of about one-third in
10-year breast cancer mortality
Standard CMF or standard 4AC vs no
adjuvant chemotherapy: RR = 0.75-0.80
More effective regimen* vs
standard CMF or 4AC: RR = 0.80-0.85
More effective regimen* vs no adjuvant
chemotherapy: RR is approximately 0.64
(as 0.775 x 0.825 = 0.64), corresponding to a
reduction of about one-third in 10-year risk
* eg, CAF or CEF (or taxane plus 4AC)
EBCTCG, Lancet 2011
Trials of chemotherapy vs
no adjuvant chemotherapy
- Any anthracycline-based regimen
(eg, standard 4AC) vs nil
- Standard CMF vs nil
EBCTCG, Lancet 2011
Breast cancer mortality ratio: any anthracycline-based
regimen (eg, standard 4AC) vs no adjuvant chemotherapy,
by ER STATUS and subsets of ER+
EBCTCG, Lancet 2011
Halving big risks and halving
small risks by chemotherapy
• Proportional risk reduction does not depend
much on age, ER status or nodal status
(or on tumour grade or tumour diameter)
• Absolute risk reduction, however, depends
on the prognosis – and, for ER+ disease,
this is the prognosis with endocrine therapy
• Information lacking on tumour gene expression
and on quantitative immunohistochemistry
EBCTCG, Lancet 2011
EBCTCG, 1984-2012: Several moderate survival gains
from successive improvements in local treatment,
in endocrine therapy and in chemotherapy
EBCTCG, 2012-15: All breast screening trialists have
agreed to collaborate by sending individual patient
data for central checks & collaborative re-analyses to
assess proportional mortality reductions in old trials
(some of which were reported better than others)